Compounds of the general formula ##STR2## wherein R.sup.3 is a residue of an electrophile suitable for the substitution of lithiated benzene derivatives, are valuable intermediates which can be used for the manufacture of a wide variety of products. For example, they can be used for the manufacture of pharmaceutically active substances which have as a structural feature a 2,4-bis- (trifluoromethyl)phenyl group, e.g. for the manufacture of 4-[(Z)-2,4-bis(trifluoromethyl)styryl]-4,8-dimethyl-2,3-dioxabicyclo[3.3.1 ]nonan-7-one which is described in European Patent Publication No. 311 955 and which can be used for the prevention or control of malaria.
The lithiation of 1,3-bis(trifluoromethyl)benzene and the reaction of the solution obtained with electrophiles are known reactions. See K. Kodaira et al. in Bull. Chem. Soc. 61, 1625-1631 (1988) (document A), J. P. Coleman et al. in J. Chem. Soc. Perkin I 1973, 1903 et seq. (document B) and P. Aeberli et al. in J. Organomet. Chem. 67, 321-325 (1974) (document C). The lithiation of 1,3-bis(trifluoromethyl)benzene with n-butyllithium and the reaction of the solutions obtained with electrophiles, namely with elemental bromine or solid carbon dioxide, are described in these publications. The products obtained from these reactions are mixtures of bis(trifluoromethyl)-bromobenzenes or, bis(trifluoromethyl)-benzoic acids, which consist essentially of the corresponding 2,4-isomers and of the corresponding 2,6-isomers, i.e. the lithiation and the subsequent reaction with the electrophiles takes place mainly in the 2-position and in the 4-position of the 1,3-bis(trifluoromethyl)benzene. Table I gives the compositions of the mixtures obtained from the reactions described in these publications.
TABLE I ______________________________________ Amount of isomers in % Electro- 2,4- 2,6- other Document phile R.sup.3 isomer isomer isomers ______________________________________ Document A Br.sub.2 Br 47.5 45.1 7.4 Document A " " 47.3 42.4 10.3 Document B CO.sub.2 solid --COOH 56.3 35.0 8.7 Document C " " 60.0 40.0 -- Document C " " 62.0 38.0 -- Document C " " 59.0 41.0 -- ______________________________________
As can be concluded from this Table, the ratio of 2,4-isomer to 2,6-isomer in the products obtained varies between about 1:1 and 3:2 in favour of the 2,4-isomers.